Undesired coagulation of blood often complicates blood-processing procedures such as hemofiltration, hemodialysis, and hemodiafiltration, particularly where a filter is used. Blood generally coagulates by transforming soluble fibrinogen into insoluble fibrin by activation of numerous circulating proteins that interact in a cascading series of limited proteolytic reactions. At each step of reaction, a clotting factor undergoes limited proteolysis and becomes an active protease that in turn activates the next clotting factor until finally a solid fibrin clot is formed. Fibrinogen (factor I) is activated by thrombin (factor IIa), which is converted from prothrombin by activated factor X. There are two separate coagulation pathways that activate factor X—the intrinsic system and the extrinsic system. Activation of the extrinsic system requires tissue thromboplastin (factor III), which is released from damaged tissue into the circulating blood to activate clotting. The intrinsic system, on the other hand, has all the factors necessary for coagulation contained in the circulating blood. The intrinsic system is, for example, partially responsible for clotting of blood in a test tube. Aggregation of platelets caused by stagnation of blood also facilitates blood coagulation.
During hemofiltration, for example, blood is removed from the patient, filtered through a filtering column to remove waste products, and returned to the patient's circulation. However, during removal of waste products, fluid is also removed, causing concentration of blood leaving the outflow tubing. As a result of hemoconcentration, hematocrit rises, and the intrinsic coagulation pathway and platelets are activated causing clotting of blood around the outlet of the filtering column, thereby compromising the hemofiltrating process.
What is needed are devices and methods that can be used with a filtering column during blood-processing procedures, such as hemofiltration, hemodialysis, hemodiafiltration, and peritoneal dialysis, to prevent clotting. Existing devices are inadequate for this purpose.